title: Docosahexaenoic acid augments hypothermic neuroprotection in a neonatal rat asphyxia model.
abstract: BACKGROUND
  In neonatal rats, early post-hypoxia-ischemia (HI) administration of the omega-3 fatty acid docosahexaenoic acid (DHA) improves sensorimotor function, but does not attenuate brain damage.
  
  
  OBJECTIVE
  To determine if DHA administration in addition to hypothermia, now standard care for neonatal asphyxial brain injury, attenuates post-HI damage and sensorimotor deficits.
  
  
  METHODS
  Seven-day-old (P7) rats underwent right carotid ligation followed by 90 min of 8% O2 exposure. Fifteen minutes later, pups received injections of DHA 2.5 mg/kg (complexed to 25% albumin) or equal volumes of albumin. After a 1-hour recovery, pups were cooled (3 h, 30°C). Sensorimotor and pathology outcomes were initially evaluated on P14. In subsequent experiments, sensorimotor function was evaluated on P14, P21, and P28; histopathology was assessed on P28.
  
  
  RESULTS
  At P14, left forepaw function scores (normal: 20/20) were near normal in DHA + hypothermia-treated animals (mean ± SD 19.7 ± 0.7 DHA + hypothermia vs. 12.7 ± 3.5 albumin + hypothermia, p < 0.0001) and brain damage was reduced (mean ± SD right hemisphere damage 38 ± 17% with DHA + hypothermia vs. 56 ± 15% with albumin + hypothermia, p = 0.003). Substantial improvements on three sensorimotor function measures and reduced brain damage were evident up to P28.
  
  
  CONCLUSIONS
  Unlike post-HI treatment with DHA alone, treatment with DHA + hypothermia produced both sustained functional improvement and reduced brain damage after neonatal HI.
authors.affiliation: Department of Obstetrics and Gynecology; Division of Maternal Fetal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Deborah R
authors.initials: DR
authors.lastname: Berman
authors.affiliation: Department of Obstetrics and Gynecology; Division of Maternal Fetal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Ellen
authors.initials: E
authors.lastname: Mozurkewich
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor, Michigan USA.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor, Michigan USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Shangguan
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor, Michigan USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Barks
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor, Michigan USA.|Department of Neurology, University of Michigan, Ann Arbor, Michigan USA.
authors.forename: Faye S
authors.initials: FS
authors.lastname: Silverstein
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000628:therapy*; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D001927:Brain Diseases / Q000517:prevention & control; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000008:administration & dosage*; D005260:Female; D018737:Hand Strength; D007036:Hypothermia, Induced; D020925:Hypoxia-Ischemia, Brain / Q000628:therapy; D008297:Male; D018696:Neuroprotective Agents; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018696:Neuroprotective Agents; D004281:Docosahexaenoic Acids